Vitamin B compounds, such as niacinamide, are well known cosmetic skin care agents that are believed to provide a variety of skin care benefits (see, e.g., Bissett et al. “Niacinamide: A B Vitamin that Improves Aging Facial Skin Appearance” and Draelos “Clinical Situations Conducive to Proactive Skin Health and Anti-Aging Improvement”). Some of the reported benefits include improvement in the appearance of facial skin texture, red blotchiness, hyperpigmentation, and the enhancement of skin barrier function. Given these benefits, there is a continuing desire to increase the amount of vitamin B compounds delivered into human skin from topically applied cosmetic compositions to further enhance the skin benefits provided by these compounds.
It is known that a rate limiting step in the percutaneous absorption of ingredients is their initial penetration into and across the stratum corneum, see, e.g., Suhonen et al., “Chemical Enhancement of Percutaneous Absorption In Relation To Stratum Corneum Structural Alterations”, Suhonen et al., Journal of Controlled Release, 59 (1999), pgs 149-161. Suhohen et al. also observed that there are at least two potential pathways thru the stratum cornenum: 1) transcellular (i.e., across the corneocytes and the lipid matrix), and 2) intercellular (i.e., via the lipid domains between the corneocytes), with the intercellular route believed to be providing the principal route for the permeation of ingredients.
Skin penetration enhancers are well known. As far back as 1997, a literature review by Osborne et al. purported to find more than 275 chemical compounds cited as enhancing skin permeation (see, e.g., Osborne, David, “Skin Penetration Enhancers Cited in the Technical Literature, Pharmaceutical Technology”, 1997, pp 58-66). Compounds identified by Osborne include various species of fatty alcohols, fatty acid esters, fatty acids, fatty alcohol ethers, enzymes, amines and amides, surfactants, n-methyl pyrrolidones, ionic compounds and various others. More recently, Williams et al. noted that “[n]umerous compounds have been evaluated for penetration enhancing activity, including sulphoxides (such as dimethylsulphoxide, DMSO), azones (e.g., laurocapram), pyrrolidones, (for example 2-pyrrolidone, 2P), alcohols and alkanols (ethanol, or decanol), glycols (for example propylene glycol, PG, a common excipient in topically applied dosage forms), surfactants (also common in dosage forms) and terpenes”. Williams et al., “Penetration Enhancers”, Advanced Drug Delivery Reviews 56, pgs 603-618 (2004), see also, Pathan et al., “Chemical Penetration Enhancers for Transdermal Drug Delivery Systems”, Tropical Journal of Pharmaceutical Research, Vol. 8(2), pgs 173-179 (2009).
While various skin penetration enhancers are known, their mechanisms of action, particularly in the stratum corneum, are still being investigated. For example, Suhonen et al. postulated that “many penetration enhancers are capable of inserting between the hydrophobic tails of the bilayer, thus disturbing their packing, increasing their fluidity and, subsequently, leading to easier diffusion of lipid-like penetrants”. Suhonen et al. also concluded however that “[a]lthough during the last 10 years an enormous amount of knowledge became available on the structure of the stratum corneum and the effect of solvent and penetration enhancers on this structure, still our knowledge on this tissue and its lipid organization is very limited”. Similarly, Williams et al. noted in 2004 that the inclusion of penetration enhancers “into topical or transdermal formulations is limited since the underlying mechanisms of action of these agents are seldom clearly defined”. Even more recently, Williams and Barry, “Penetration enhancers”, Advanced Drug Delivery Reviews, Vol. 64, pgs 128-137 (2012), stated that “[i]t is difficult to select rationally a penetration enhancer for a given permeant.” While the effects of certain individual ingredients on skin penetration has been studied to some degree, the role that combinations of ingredients might play in enhancing penetration of cosmetic agents into and thru the stratum corneum appears to be even less well studied, including how varying concentrations, ratios and/or combinations of ingredients might affect penetration of cosmetic skin ingredients.